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Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/96367
Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization
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A limited repertoire of PPP family of serine/threonine phosphatases with a highly conserved catalytic domain acts on thousands of protein targets to orchestrate myriad central biological roles. A major structural reorganization of human calcineurin, a ubiquitous Ser/Thr PPP regulated by calcium and calmodulin and targeted by immunosuppressant drugs cyclosporin A and FK506, is unveiled here. The new conformation involves trans- to cis- isomerization of proline in the SAPNY sequence, highly conserved across PPPs, and remodels the main regulatory site where NFATc transcription factors bind. Transitions between cis- and trans- conformations may involve peptidyl prolyl isomerases such as cyclophilin A and FKBP12, which are known to physically interact with and modulate calcineurin even in the absence of immunosuppressant drugs. Alternative conformations in PPPs provide a new perspective on interactions with substrates and other protein partners and may foster development of more specific inhibitors as drug candidates.
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GUASCH, Alicia, et al. Calcineurin Undergoes a Conformational Switch Evoked via Peptidyl-Prolyl Isomerization. PLoS One. 2015. Vol. 10, núm. 8, pàgs. e0134569-e0134569. ISSN 1932-6203. [consulta: 8 de maig de 2026]. Disponible a: https://hdl.handle.net/2445/96367